Table 1.
SNP | CHR | Gene symbol | P value (n = 115) in stage I | P value (n = 31) in stage IIa | P value (n = 32) in stage IIb | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
PRU >208 | PRU | H4 C2h | Clop Tmax | Clop Cmax | Clop AUC0‐4h | H4 Tmax | H4 Cmax | H4 AUC0‐4h | ||||
rs74460025 | 5 | GABRB2 | 2.61 × 10‐5 | 5.08 × 10‐3 | 5.19 × 10‐3 | 0.679 | 0.973 | 0.672 | 0.760 | 0.740 | 0.668 | 0.9402 |
rs17145154 | 7 | DNAH11 | 4.72 × 10‐5 | 6.36 × 10‐4 | 2.40 × 10‐2 | 0.672 | 0.557 | 0.799 | 0.0513 | 0.950 | 0.794 | 0.4269 |
rs4741806 | 9 | Intergenic | 4.04 × 10‐4 | 6.28 × 10‐5 | 2.40 × 10‐3 | 0.972 | 0.483 | 0.544 | 0.495 | 0.918 | 0.541 | 0.9502 |
rs1048196 | 10 | HELLS | 1.45 × 10‐5 | 4.05 × 10‐5 | 4.20 × 10‐4 | 0.978 | 0.402 | 0.587 | 0.742 | 0.248 | 0.0273 | 0.0135 |
rs1926711 | 10 | CYP2C18 | 8.24 × 10‐6 | 3.51 × 10‐5 | 6.61 × 10‐3 | 0.667 | 0.153 | 0.291 | 0.773 | 0.517 | 0.0843 | 0.0153 |
rs4244285 | 10 | CYP2C19 | 1.66 × 10‐5 | 6.01 × 10‐5 | 2.20 × 10‐4 | 0.955 | 0.125 | 0.205 | 0.842 | 0.172 | 0.00861 | 0.0334 |
rs2852213 | 11 | GRIK4 | 8.77 × 10‐5 | 5.12 × 10‐3 | 1.62 × 10‐2 | 0.593 | 0.147 | 0.0794 | 0.121 | 0.679 | 0.495 | 0.9842 |
rs774392 | 12 | GRIP1 | 2.49 × 10‐5 | 3.18 × 10‐4 | 6.72 × 10‐3 | 0.432 | 0.444 | 0.369 | 0.382 | 0.611 | 0.387 | 0.961 |
rs12913988 | 15 | ATP10A | 1.57 × 10‐3 | 9.69 × 10‐6 | 1.47 × 10‐2 | 0.307 | 0.831 | 0.691 | 0.895 | 0.538 | 0.617 | 0.9948 |
rs12456693 | 18 | SLC14A2 | 6.83 × 10‐5 | 1.07 × 10‐2 | 8.52 × 10‐3 | 0.00485 | 0.262 | 0.172 | 0.0444 | 0.0245 | 0.129 | 0.4131 |
rs1571678 | 21 | N6AMT1 | 1.21 × 10‐3 | 2.65 × 10‐5 | 6.85 × 10‐3 | 0.0249 | 0.969 | 0.958 | 0.0551 | 0.286 | 0.358 | 0.0643 |
rs2254638 | 21 | N6AMT1 | 1.87 × 10‐3 | 5.37 × 10‐5 | 6.29 × 10‐3 | 0.0249 | 0.969 | 0.958 | 0.0551 | 0.286 | 0.358 | 0.0386 |
rs17209532 | 22 | Intergenic | 2.46 × 10‐3 | 1.92 × 10‐5 | 3.08 × 10‐2 | 0.218 | 0.266 | 0.167 | 0.0670 | 0.520 | 0.306 | 0.7581 |
rs7292279 | 22 | Intergenic | 7.39 × 10‐4 | 4.34 × 10‐5 | 9.08 × 10‐3 | 0.730 | 0.689 | 0.863 | 0.385 | 0.944 | 0.860 | 0.1483 |
rs13123057 | 4 | UGT2B11 | 8.69 × 10‐3 | 8.94 × 10‐3 | 8.69 × 10‐4 | 0.334 | 0.984 | 0.847 | 0.332 | 0.396 | 0.850 | 0.7324 |
rs12369968 | 12 | MGST1 | 3.43 × 10‐4 | 3.57 × 10‐3 | 9.18 × 10‐4 | 0.459 | 0.440 | 0.448 | 0.131 | 0.0904 | 0.135 | 0.9919 |
rs2487032 | 9 | ABCA1 | 3.46 × 10‐3 | 3.75 × 10‐2 | 5.34 × 10‐3 | 0.243 | 0.0211 | 0.00590 | 0.0189 | 0.382 | 0.329 | 0.8812 |
rs4147820 | 1 | ABCA4 | 1.74 × 10‐3 | 8.42 × 10‐4 | 7.00 × 10‐3 | 0.495 | 0.448 | 0.604 | 0.759 | 0.673 | 0.679 | 0.662 |
AUC, area under the curve; Clop, clopidogrel; Cmax, peak plasma concentration; PRU, P2Y12 reaction unit; SNP, single‐nucleotide polymorphism; Tmax, time of maximum plasma concentration.
SNPs were associated with PRU or PRU >208 (P < 1 × 10−4) and CH4 at 2 h (P < 0.01), or SNPs in absorption, distribution, metabolism, and excretion gene were associated with PRU or PRU >208 (P < 0.05) and CH4 (P < 0.01) in stage I.
SNPs in bold indicate associations with pharmacokinetic parameters of clopidogrel or its active metabolite H4 in stage IIa.